碱性成纤维细胞生长因子对动脉粥样硬化大鼠脑基底动脉血管内皮功能与结构的影响

Effects of basic fibroblast growth factor on endothelial function and structure of the basilar artery of atherosclerotic rats

目的探讨碱性成纤维细胞生长因子(bFGF)对动脉粥样硬化(AS)模型大鼠脑基底动脉血管内皮功能与结构的影响。方法将48只雄性Wistar大鼠随机平均分成正常对照组、AS组与bFGF治疗组。除正常对照组外,在喂食开始时一次性腹腔注射维生素D3(6×105IU/kg)加高脂配方饲料喂养,6周后bFGF治疗组采用腹腔注射bFGF(9.5μg/kg,2次/d)治疗,连续2周后处死。观察不同组离体基底动脉对不同浓度乙酰胆碱(Ach)的舒张反应率;光镜观察血管形态结构的变化;ELISA与比色法分别测定血管壁一氧化氮(NO)与血清血管内皮生长因子(VEGF)含量变化;MTT法测体外培养内皮细胞的增殖活性;鬼笔环肽染色观察培养平滑肌细胞骨架微丝的变化。结果高脂饲料饲养6周后早期动脉粥样硬化形成;与AS组相比,经bFGF治疗2周后基底动脉对不同浓度Ach舒张反应百分率、动脉管壁NO与血清VEGF含量明显升高(P<0.05);血管内皮细胞增殖活性也显著增强(P<0.05);平滑肌细胞骨架微丝损伤明显改善。结论 AS对基底动脉血管内皮造成了损伤,而bFGF参与了损伤动脉血管结构与内皮功能的调节,这些变化提示bFGF对脑血管具有明显的保护作用。

Objective To study the protective effect of basic fibroblast growth factor （ bFGF ） on endothelial function and structure of the basilar artery of atherosclerotic rats .Methods A total of forty-eight male adult Wister rats were randomly divided into the normal control , the atherosclerosis （ AS） model and the bFGF treatment groups .The AS model group and the bFGF treatment group were injected with a single dose of vitamin D 3 （6 ×105 IU/kg） and loaded with high fat diet for six consecutive weeks .The bFGF （9.5μg/kg, twice one day） was injection into the abdominal cavity after six weeks in the bFGF treatment group for two weeks , and an identical volume saline was given for the AS model group and the normal control group .After eight weeks , all the rats were sacrificed .The relaxation percentages of the isolated basilar artery in response to acetylcholine （ Ach） were detected and the pathological lesions of them were observed under a light microscope .ELISA and colorimetry assayed the content of serum VEGF and basilar arterial nitric oxide （ NO） .The basilar artery was used for primary culture of both vascular endothelial cells （VECs） and vascular smooth muscle cells （VSMCs）. The influence of bFGF on the proliferation vitality of VECs was measured in vitro with MTT assay.TRITC-phalloidin labeling the cytoskeleton microfilament of VSMCs was observed by laser confocal microscopy .Results The early AS plaques were presented after six weeks by hyper lipid foods .Compared with the AS model group , the relaxation percentage of the isolated basilar artery , the content of both serum VEGF and basilar arterial NO in the bFGF treatment group were obviously increased, but the pathologic injury of the basilar artery was significantly decreased （P＆lt;0.05）.The proliferation vitality of VECs was obviously increased （P＆lt;0.05）; the cytoskeleton microfilament of VSMCs was of obviously improvement .Conclusion AS may aggravate the basilar arterial injury , but bFGF may efficiently improve the arterial endothelial function and decrease the pathological lesion of the basilar artery in the AS model rats , which may promote the arterial protective effect .